Frigostable composition for iontophoretic transdermal delivery of a triptan compound

Patent metadata

Field	Value
Publication number	US-11744806-B2
Application number	US-201816772775-A
Country	US
Kind code	B2
Filing date	Dec 13, 2018
Priority date	Dec 20, 2017
Publication date	Sep 5, 2023
Grant date	Sep 5, 2023

Abstract

The present invention relates to frigostable compositions suitable for iontophoretic transdermal delivery of a triptan compound. The inventive compositions include a salt of a triptan compound, preferably sumatriptan succinate, a polyamine, a dicarboxylic acid, and water or an aqueous solvent mixture, with the composition being free of monocarboxylic acids. The invention further relates to the use of the composition as an integral component of an iontophoretic patch, preferably as an anodic reservoir of the patch.

First claim

The invention claimed is:

1. A composition for iontophoretic transdermal delivery of a salt of a triptan compound, comprising:
a salt of a triptan compound,
a polyamine, in an amount ranging from 18 to 70%,
a dicarboxylic acid, and
water or an aqueous solvent mixture, and
wherein this composition is free of monocarboxylic acids and the water or aqueous solvent mixture is present in an amount ranging from 30 to 75 wt %.

2. The composition according to claim 1 , wherein the triptan compound is a compound that contains a 2-(1H-indol-3-yl)-N,N-dimethylethanamine moiety.

3. The composition according to claim 2 , wherein the triptan compound is almotriptan, frovatriptan, eletriptan, zolmitriptan, rizatriptan, sumatriptan or naratriptan.

4. The composition according to claim 1 , wherein the salt is a succinate.

5. The composition according to claim 1 , wherein the dicarboxylic acid is selected from C 4 to C 10 dicarboxylic acids.

6. The composition according to claim 5 wherein the dicarboxylic acid is selected from the group consisting of succinic acid, glutaric acid, adipic acid and pimelic acid.

7. The composition according to claim 1 , wherein the polyamine consists of three different methacrylate-monomers: dimethylaminoethyl-methacrylate, butylmethacrylate and methylmethacrylate.

8. The composition according to claim 7 wherein the polyamine is partially replaced by a replacement polyamine which has the following chemical structure:

with
m=5-8 and
n=2-4.

9. The composition according to claim 8 wherein the replacement polyamine is N,N-diethylamino-ethylmethacrylate methylmethacrylate copolymer.

10. The composition according to claim 1 , further comprising one or more additives.

11. An iontophoretic patch comprising the composition of claim 1 .

12. A method of iontophoretic transdermal administration of a triptan compound comprising a step of applying a composition according to claim 1 to a subject's skin, and allowing the triptan compound contained in the composition to be released therefrom and to permeate through the skin facilitated by iontophoresis and to enter the blood circulation of said subject.

13. The composition according to claim 3 , wherein the triptan compound is sumatriptan.

14. The composition according to claim 6 , wherein the dicarboxylic acid is selected from the group consisting of succinic acid and adipic acid.

15. The composition according to claim 8 , wherein m=is 6 or 7, and n=3 or 4.

16. An iontophoretic patch according to claim 11 , wherein an anodic reservoir of the patch comprises the composition of claim 1 .

17. The composition according to claim 7 , wherein the polyamine is present in an amount ranging from 18 to 30%.

18. A composition for iontophoretic transdermal delivery of a salt of a triptan compound, comprising:
a salt of a triptan compound,
a polyamine,
a dicarboxylic acid, and
water or an aqueous solvent mixture,
wherein this composition is free of monocarboxylic acids and
the polyamine is N,N-diethylamino-ethylmethacrylate methylmethacrylate copolymer, present in an amount ranging from 30 to 70%.

19. The composition according to claim 18 , wherein the composition ranges in conductivity from 5.05 to 6.14 mS/cm for compositions containing from 48.65 to 50.70% polyamide.

20. The composition according to claim 1 , wherein the composition ranges in viscosity from 504 to 2180 mPas.

21. The composition according to claim 1 , wherein the acid is adipic acid, present in an amount ranging from 3.21 to 10%.

22. The composition according to claim 1 , wherein the methacrylate is butylmethacrylate.

Assignees

• Lts Lohmann Therapie Systeme Ag
• Lts Lohmann Theraapie Systeme Ag

Inventors

• Linn Michael
• Schmitz Christoph
• Franke Hanshermann

Classifications

• A61K9/703 Primary

  characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches · CPC title

• A61K9/0009 Primary

  involving or responsive to electricity, magnetism or acoustic waves; Galenical aspects of sonophoresis, iontophoresis, electroporation or electroosmosis · CPC title

• A61K31/4045

  Indole-alkylamines; Amides thereof, e.g. serotonin, melatonin · CPC title

• A61K47/12

  Carboxylic acids; Salts or anhydrides thereof · CPC title

• A61K47/34

  Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers (A61K47/10 takes precedence) · CPC title